Exploring single-cell RNA sequencing as a decision-making tool in the clinical management of Fuchs’ endothelial corneal dystrophy

• Published in: Progress in retinal and eye research Vol. 102; p. 101286
• Main Authors: Yang, Gink N., Sun, Yu B.Y., Roberts, Philip Ke, Moka, Hothri, Sung, Min K., Gardner-Russell, Jesse, El Wazan, Layal, Toussaint, Bridget, Kumar, Satheesh, Machin, Heather, Dusting, Gregory J., Parfitt, Geraint J., Davidson, Kathryn, Chong, Elaine W., Brown, Karl D., Polo, Jose M., Daniell, Mark
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2024
• Subjects: FECD diagnostic; FECD genetics; FECD surgery; FECD therapy; scRNA-seq; FECD surgery; scRNA-seq; FECD genetics; FECD diagnostic; FECD therapy
• ISSN: 1350-9462; 1873-1635; 1873-1635
• DOI: 10.1016/j.preteyeres.2024.101286

Single-cell RNA sequencing (scRNA-seq) has enabled the identification of novel gene signatures and cell heterogeneity in numerous tissues and diseases. Here we review the use of this technology for Fuchs’ Endothelial Corneal Dystrophy (FECD). FECD is the most common indication for corneal endothelial transplantation worldwide. FECD is challenging to manage because it is genetically heterogenous, can be autosomal dominant or sporadic, and progress at different rates. Single-cell RNA sequencing has enabled the discovery of several FECD subtypes, each with associated gene signatures, and cell heterogeneity. Current FECD treatments are mainly surgical, with various Rho kinase (ROCK) inhibitors used to promote endothelial cell metabolism and proliferation following surgery. A range of emerging therapies for FECD including cell therapies, gene therapies, tissue engineered scaffolds, and pharmaceuticals are in preclinical and clinical trials. Unlike conventional disease management methods based on clinical presentations and family history, targeting FECD using scRNA-seq based precision-medicine has the potential to pinpoint the disease subtypes, mechanisms, stages, severities, and help clinicians in making the best decision for surgeries and the applications of therapeutics. In this review, we first discuss the feasibility and potential of using scRNA-seq in clinical diagnostics for FECD, highlight advances from the latest clinical treatments and emerging therapies for FECD, integrate scRNA-seq results and clinical notes from our FECD patients and discuss the potential of applying alternative therapies to manage these cases clinically. •Regulatory pathway for scRNA-seq has great potential as a clinical management tool for FECD.•Current and emerging surgical and pharmaceutical options for FECD.•ScRNA-seq can validate and safeguard emerging therapies for FECD.•Clinical workflow of using scRNA-seq as a diagnostic tool for FECD.•Latest FECD snRNA-seq results provide clinical management direction retrospectively.